A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes

Sabrina I Green; Justin R Clark; Haroldo H Santos; Kyle E Weesner; Keiko C Salazar; Saima Aslam; J William Campbell; Sarah B Doernberg; Emily Blodget; Michele I Morris; Gina A Suh; Karam Obeid; Fernanda P Silveira; Andrey A Filippov; Katrine L Whiteson; Barbara W Trautner; Austen L Terwilliger; Anthony Maresso

doi:10.1093/cid/ciad335

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes

Clin Infect Dis. 2023 Oct 13;77(8):1079-1091. doi: 10.1093/cid/ciad335.

Authors

Sabrina I Green^{1

2}, Justin R Clark¹, Haroldo H Santos¹, Kyle E Weesner¹, Keiko C Salazar¹, Saima Aslam³, J William Campbell⁴, Sarah B Doernberg⁵, Emily Blodget⁶, Michele I Morris⁷, Gina A Suh⁸, Karam Obeid⁹, Fernanda P Silveira¹⁰, Andrey A Filippov¹¹, Katrine L Whiteson¹², Barbara W Trautner^{13

14}, Austen L Terwilliger¹, Anthony Maresso¹

Affiliations

¹ Tailored Antibacterials and Innovative Laboratories for Phage (Φ) Research (TAILΦR), Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
² Laboratory of Gene Technology, KU Leuven, Leuven, Belgium.
³ Division of Infectious Diseases and Global Public Health, Center for Innovative Phage Applications and Therapeutics, University of California, San Diego, La Jolla, California, USA.
⁴ Division of Infectious Diseases and Infection Prevention, St. Luke's Hospital, Chesterfield, Missouri, USA.
⁵ Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
⁶ Department of Medicine, University of California, Irvine, California, USA.
⁷ Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
⁸ Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁹ Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
¹⁰ Division of Infection Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹¹ Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
¹² Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
¹³ Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
¹⁴ Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

Abstract

Background: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution. Reported are outcomes of customized phage therapy for patients with difficult-to-treat antimicrobial resistant infections.

Methods: We retrospectively assessed 12 cases of customized phage therapy from a phage production center. Phages were screened, purified, sequenced, characterized, and Food and Drug Administration-approved via the IND (investigational new drug) compassionate-care route. Outcomes were assessed as favorable or unfavorable by microbiologic and clinical standards. Infections were device-related or systemic. Other experiences such as time to treatment, antibiotic synergy, and immune responses were recorded.

Results: Fifty requests for phage therapy were received. Customized phages were generated for 12 patients. After treatment, 42% (5/12) of cases showed bacterial eradication and 58% (7/12) showed clinical improvement, with two-thirds of all cases (66%) showing favorable responses. No major adverse reactions were observed. Antibiotic-phage synergy in vitro was observed in most cases. Immunological neutralization of phages was reported in 5 cases. Several cases were complicated by secondary infections. Complete characterization of the phages (morphology, genomics, and activity) and their production (methods, sterility, and endotoxin tests) are reported.

Conclusions: Customized phage production and therapy was safe and yielded favorable clinical or microbiological outcomes in two-thirds of cases. A center or pipeline dedicated to tailoring the phages against a patient's specific AMR bacterial infection may be a viable option where standard treatment has failed.

Keywords: antibiotic resistance; microbiology; phage; phage therapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Anti-Bacterial Agents / therapeutic use
Bacteria
Bacterial Infections* / microbiology
Bacterial Infections* / therapy
Bacteriophages* / physiology
Humans
Phage Therapy*
Retrospective Studies

Substances

Anti-Bacterial Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding